尿苷胞苷激酶2在肿瘤中的作用及其抑制剂研究进展

doi:10.12092/j.issn.1009-2501.2026.03.008

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (3): 362-371.doi: 10.12092/j.issn.1009-2501.2026.03.008

尿苷胞苷激酶2在肿瘤中的作用及其抑制剂研究进展

张佳炜¹(), 马雪含², 肖恩浩², 范思邈³^,*(), 柳丹阳⁴^,*()

1. 沈阳药科大学制药工程学院，沈阳 110016，辽宁
2. 沈阳药科大学中药学院，沈阳 110016，辽宁
3. 天津中医药大学中药学院，天津 301617
4. 沈阳药科大学临床药学院，沈阳 110016，辽宁

收稿日期:2025-05-07 修回日期:2026-01-30 出版日期:2026-03-26 发布日期:2026-04-03
通讯作者: 范思邈,柳丹阳 E-mail:1928359378@qq.com;fansimiao@tjutcm.edu.cn;liudy001@126.com
作者简介:张佳炜，女，研究方向：抗肿瘤药物研发与机制探索。E-mail：1928359378@qq.com
基金资助:
国家自然科学基金（81973528）；天津市教委科研计划项目（2019KJ073）；辽宁省教育厅科研项目（LJ212410163019）

Uridine cytidine kinase 2's function in tumors and the ongoing research on its inhibitors

Jiawei ZHANG¹(), Xuehan MA², Enhao XIAO², Simiao FAN³^,*(), Danyang LIU⁴^,*()

1. School of Pharmaceutical Engineering
2. School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
3. School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
4. School of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China

Received:2025-05-07 Revised:2026-01-30 Online:2026-03-26 Published:2026-04-03
Contact: Simiao FAN,Danyang LIU E-mail:1928359378@qq.com;fansimiao@tjutcm.edu.cn;liudy001@126.com

摘要/Abstract

摘要：

尿苷胞苷激酶2（uridine cytidine kinase 2，UCK2）是嘧啶补救合成通路的限速酶。研究证实，UCK2在多种肿瘤中表达上调，且与预后不良密切相关。UCK2不仅具有激酶的催化功能，还能直接参与细胞信号转导的非催化功能。UCK2一方面通过催化核苷酸的大量合成，为肿瘤细胞快速增殖提供支持；另一方面能调控多条信号通路，进而影响肿瘤的发生与发展。因此，UCK2是极具潜力的癌症治疗靶点，探索其在肿瘤发生发展中的作用及相关抑制剂研发，具有重要临床意义。目前，针对UCK2的抑制剂主要分为两类：一类是靶向酶催化功能的核苷酸类似物竞争性抑制剂，另一类是靶向其细胞信号转导非催化功能的非竞争性抑制剂。此外，本文通过数据库检索与分子对接技术，筛选出可能与UCK2相互作用的分子，并评估了这些分子与UCK2的结合能力。综上，本文综述了UCK2在癌症中的作用及机制，同时总结了抑制UCK2生物学功能的化合物开发及其作用机制的研究进展。

关键词: 尿苷胞苷激酶2, 癌症治疗靶点, 核苷酸合成, 生物标志物, 尿苷胞苷激酶2抑制剂

Abstract:

Uridine cytidine kinase 2 (UCK2) is the rate-limiting enzyme in the pyrimidine salvage synthesis pathway. Recent studies have shown that UCK2 is overexpressed in a variety of tumors and is associated with poor prognosis. In addition to its catalytic function as a kinase, UCK2 also plays a non-catalytic role in cellular signal transduction. UCK2 can not only support the rapid proliferation of tumor cells by catalyzing nucleotide synthesis, but also regulate various signaling pathways, thereby affecting the occurrence and development of tumors. Therefore, UCK2 is a promising target for cancer therapy, and it is of great clinical significance to explore its role in tumorigenesis and development and the development of related inhibitors. Now, the UCK2 inhibitors mainly include two categories: one is based on nucleotide analogs, which are competitive inhibitors of this enzyme’s catalytic function, and the other is based on non-competitive inhibitors that target the catalytic function of signal transduction. In addition, based on the database and molecular docking, we explore the molecules that may interact with UCK2 and their binding ability with UCK2. In conclusion, this review summarizes the roles and mechanisms of UCK2 in cancer, and the progress in the development of compounds that inhibit the biological functions of UCK2 and the mechanisms.

Key words: UCK2, cancer treatment targets, nucleotide synthesis, biomarkers, UCK2 inhibitor

中图分类号:

张佳炜, 马雪含, 肖恩浩, 范思邈, 柳丹阳. 尿苷胞苷激酶2在肿瘤中的作用及其抑制剂研究进展[J]. 中国临床药理学与治疗学, 2026, 31(3): 362-371.

Jiawei ZHANG, Xuehan MA, Enhao XIAO, Simiao FAN, Danyang LIU. Uridine cytidine kinase 2's function in tumors and the ongoing research on its inhibitors[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(3): 362-371.

图/表 6

图 1

Fig.1 Structure of UCK2 (taking chain A as an example)

图 2

Fig.2 UCK2 expression levels in normal tissues and tumor tissues blue represents normal samples, red represents tumor samples.

图 3

Fig.3 Structural formulas of small-molecule inhibitors of UCK2

图 4

Fig.4 Structural formulas of small molecules that may bind to UCK2 (predicted by databases)

表 1

Table 1 Docking energies between seven compounds and UCK2 (PDB ID: 1xrj)

Compound	Energy (kcal/mol)
Ara-CTP	?135.352
Poly-C	?135.248
Uridylate	?132.318
MgADP	?125.766
Citric acid	?123.328
Uridine	?114.914
Cytidine	?111.85

图 5

Fig.5 Molecular docking results between UCK2 (PDB ID: 1xrj) and seven compounds

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尿苷胞苷激酶2在肿瘤中的作用及其抑制剂研究进展

Uridine cytidine kinase 2's function in tumors and the ongoing research on its inhibitors

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